Fig. 5
From: Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus
Identification of key residues for fungal selectivity. a The locations of secondary structural features observed in the respective radicicol and CMLD013075 co-crystal structures presented in Fig. 4a are mapped above the primary sequence alignments. Red shading indicates areas of complete sequence conservation. Black arrowheads indicate the position of the amino acids (shaded in yellow) that were changed for experiments involving mutagenesis. Positions with variation are indicated in red letters when a particular amino acid is most common and black letters when the position is variable. b Localization of residues mutated to examine effects on compound binding. Altered amino acids are represented as brick-colored spheres in the C. albicans NBD-CMLD013075 co-complex structure. Side chains of each residue are depicted. The ligand is represented as sticks and color-coded according to heteroatom composition. Light red spheres represent oxygen atoms. c Inhibitor sensitivity of isogenic S. cerevisiae strains engineered to express the indicated wild-type and mutant Hsp90 proteins as their sole source of Hsp90. Relative growth inhibition by twofold serial dilutions of radicicol (top) or oxime derivative CMLD013075 (bottom) is displayed in the same manner as in Fig. 3. Each colored box represents the mean of duplicate determinations. Color scale for relative growth is provided, green: no inhibition to black: complete inhibition. The experiment was repeated as an independent biological replicate to confirm results
